AG-120 or AG-221 Combination Therapy for Acute Myeloid Leukemia

Recruiting in Palo Alto (17 mi)

+16 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Institut de Recherches Internationales Servier

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this Phase I, multicenter, clinical trial is to evaluate the safety of AG-120 and AG-221 when given in combination with standard AML induction and consolidation therapy. The study plans to evaluate up to 2 dose levels of AG-120 in participants with an isocitrate dehydrogenase protein 1 (IDH1) mutation and up to 2 dose levels of AG-221 in participants with an isocitrate dehydrogenase protein 2 (IDH2) mutation. AG-120 or AG-221 will be administered with 2 types of AML induction therapies (cytarabine with either daunorubicin or idarubicin) and 2 types of AML consolidation therapies (mitoxantrone with etoposide \[ME\] or cytarabine). After consolidation therapy, participants may continue on to maintenance therapy and receive daily treatment with single-agent AG-120 or AG-221 until relapse, development of an unacceptable toxicity, or hematopoietic stem cell transplant (HSCT). The study will end when all participants have discontinued study treatment.

Eligibility Criteria

Adults with newly diagnosed Acute Myeloid Leukemia (AML) having specific mutations (IDH1/IDH2), who haven't had AML treatment but may have been treated for related conditions. They should be in a stable health condition, not pregnant or breastfeeding, and willing to use effective contraception.

Inclusion Criteria

I have AML with an IDH mutation and haven't started treatment yet.

My kidney function is within normal ranges.

I am eligible for initial and follow-up cancer treatments.

See 6 more

Exclusion Criteria

I am not on strong CYP3A4 inducers, or it can be managed.

I have had chemotherapy for AML, but hydroxyurea might be an exception.

I do not have any uncontrolled infections or fungal infections.

See 11 more

Treatment Details

Interventions

AG-120 (IDH Inhibitor)
AG-221 (IDH Inhibitor)
Cytarabine (Antimetabolite)
Daunorubicin (Topoisomerase II Inhibitor)
Etoposide (Topoisomerase II Inhibitor)
Idarubicin (Topoisomerase II Inhibitor)
Mitoxantrone (Topoisomerase II Inhibitor)

Trial OverviewThe trial is testing AG-120 or AG-221 combined with standard AML therapies during different phases of treatment. It aims to find the safest doses of these drugs when used with induction and consolidation therapy, followed by maintenance until relapse or unacceptable toxicity.

Participant Groups

6Treatment groups

Experimental Treatment

Group I: AG-221 with cytarabine and idarubicinExperimental Treatment5 Interventions

Daily AG-221 administered orally in combination with standard Induction therapy and consolidation therapy. After 1 cycle of induction therapy, participants may undergo a second induction cycle given as per institutional practice. Participants who achieve an adequate response at the end of induction therapy will go on to receive consolidation therapy (mitoxantrone/etoposide or up to 4 cycles of cytarabine) in combination with AG-221. Participants who complete consolidation therapy and are in CR or CRi (including CRp) may continue on maintenance therapy and receive daily treatment with AG-221.

Group II: AG-221 with cytarabine and daunorubicinExperimental Treatment5 Interventions

Group III: AG-221 (starting on Day 8) with cytarabine and idarubicinExperimental Treatment5 Interventions

Daily AG-221 administered orally starting on Day 8 of induction cycle 1 in combination with standard Induction therapy and consolidation therapy. After 1 cycle of induction therapy, participants may undergo a second induction cycle given as per institutional practice. Participants who achieve an adequate response at the end of induction therapy will go on to receive consolidation therapy (mitoxantrone/etoposide or up to 4 cycles of cytarabine) in combination with AG-221. Participants who complete consolidation therapy and are in CR or CRi (including CRp) may continue on maintenance therapy and receive daily treatment with AG-221.

Group IV: AG-221 (starting on Day 8) with cytarabine and daunorubicinExperimental Treatment5 Interventions

Group V: AG-120 with cytarabine and idarubicinExperimental Treatment5 Interventions

Daily AG-120 administered orally in combination with standard Induction therapy and consolidation therapy. After 1 cycle of induction therapy, participants may undergo a second induction cycle given as per institutional practice. Participants who achieve an adequate response at the end of induction therapy will go on to receive consolidation therapy (mitoxantrone/etoposide or up to 4 cycles of cytarabine) in combination with AG-120. Participants who complete consolidation therapy and are in CR or CRi (including CRp) may continue on maintenance therapy and receive daily treatment with AG-120.

Group VI: AG-120 with cytarabine and daunorubicinExperimental Treatment5 Interventions

Daily AG-120 administered orally in combination with standard Induction therapy and consolidation therapy. After 1 cycle of induction therapy, participants may undergo a second induction cycle given as per institutional practice. Participants who achieve an adequate response at the end of induction therapy will go on to receive consolidation therapy (mitoxantrone/etoposide or up to 4 cycles of cytarabine) in combination with AG-120. Participants who complete consolidation therapy and are in complete response (CR) or complete remission with incomplete hematologic recovery (CRi) (including CR with incomplete platelet recovery \[CRp\]) may continue on maintenance therapy and receive daily treatment with AG-120.

AG-120 is already approved in United States for the following indications:

🇺🇸 Approved in United States as Tibsovo for: